Back in 2018, when we could still freely travel the world for scientific collaboration, our lab was approached by a colleague in the UK interested in a new drug discovery collaboration.  Dr. Alan Morgan, Professor of Cellular and Molecular Physiology at the University of Liverpool, contacted our group about profiling a repurposed compound his laboratory had identified in a screening assay using C. elegans and zebrafish. The project would involve training his graduate student, Alistair Jones, to conduct the in vivo drug screening of the repurposed compound, chlorothymol, in our group’s well-established mouse seizure and epilepsy models. The scientific goal was ultimately to validate the screening approach in C. elegans and zebrafish in use in their laboratory in the UK so as to accelerate the discovery of new agents for the treatment of epilepsy.

Alistair Jones submitted and was successfully awarded a research grant to come to our lab in Seattle from the UK. Roughly 7 months later (February 2019), Alistair arrived to begin his 8 weeks of training in our lab working with mice for the very first time in his scientific career! His chances to work with mice in his home country are somewhat restricted due to the limitations on vertebrate animal work. Therefore, this time became his first chance to perform behavioral work in a mammalian system.

One of the most exciting things about embarking on a new research proposal is that we have no idea where the project will go. We were setting off into the unknown! While we had original planned for a core set of acute seizure model studies, ultimately the data pointed us down a new road that was unexpected. Alistair and I met weekly to review his data, determine next steps, and discuss implications in the broader context of antiseizure drugs currently available today. In the end, chlorothymol, was found to be protective in several mouse seizure models, including the 6‐Hz 44‐mA model of pharmacoresistant seizures.

Our work in mice confirmed that chlorothymol was a validate candidate for further evaluation for the treatment of epilepsy. This work was published in Epilepsia in August 2020. Further, this cross continent collaboration demonstrated that C. elegans, zebrafish, and rodents can be strategically combined in a drug screening program to accelerate, and potentially de-risk, the identification of novel therapeutics. While the concept of using reduced systems for epilepsy drug discovery was pioneered by Scott Baraban at UCSF, our work is the first to combine the invertebrate screening approach with well-established rodent seizure and epilepsy models and profiling in excised patient tissues. In the future, we are hopeful to perform further screening with novel candidate compounds and advance these agents to the clinic.